6. Project Summary / Abstract The goal of this project is to study prospectively the development of social visual engagement in infants with autism spectrum disorders (ASD) by means of eye-tracking technology and innovative quantification of visual attention during viewing of naturalistic social situations. We will measure (1) visual fixation time during viewing of adults engaged in infant-directed approaches, and (2) temporally-sensitive visual scanning patterns during viewing of infants engaged in play. Experimental data will be collected at 2, 4, 6, 9, 12, 18, and 24 months. A cohort of 235 infants will be enrolled in this project, consisting of infant siblings of children with autism who are at High Risk for developing an ASD (HR-ASD, N=135); infants at High Risk for Developmental Delays without familial history of ASD (HR-DD, N=50); and children at Low Risk of developmental problems with Typical Development expected (LR-TDexpected, N=50). Confirmatory diagnostic assessment will take place at 36 months. The primary analyses will focus on comparisons between children who develop an ASD in comparison with DD and TD children. Given the familial nature of ASD and the potential for advancing research on mediating phenotypes, comparisons will also be made between all siblings of children with ASD (entire HR-ASD sample) in relation to the HR-DD and LR-TDexpected groups. This work builds on our findings of anomalous visual fixation patterns to dynamic social stimuli in adolescents (R01 HD04217) and in 24- to 36-month-olds (U54 MH66494, Yale STAART) with ASD. In both cases, summaries of visual fixation on regions of interest (eyes, mouth, body, & object) were strong predictors of concurrent, standardized measures of social disability. Here we extend this work in two ways: (1) we will employ novel group measures of moment-by-moment visual scanning behavior developed by our lab which are particularly sensitive to time-delimited social and physical cues occurring naturally in infants' surrounding environment; and (2) we will quantify the ontogeny of a key mechanism of socialization and its hypothesized derailment in the early pathogenesis of ASD by studying longitudinally a group of infants at greater risk for developing the disorder. We capitalize on a project focused on the detailed clinical characterization of the same cohort (Project 1, PO1 HD003008), and on the conceptual and technological advancements resulting from our continuing studies of young children with ASD (Project 1, P50 HD055726). Our programmatic goals are to (1) study early mechanisms of socialization and the role of these mechanisms in the heterogeneity of syndrome expression in ASD; and (2) to develop performance-based measures capable of predicting developmental and diagnostic outcome and able to serve as screening protocols for infants at risk for ASD. This project addresses several key action items of the NIH Interagency Autism Coordinating Committee, with emphasis on developmental markers and screening in infants, and neurodevelopmental processes. 7. Project Narrative In this project we will map and quantify the unfolding of social visual engagement from 2 to 24 months of age, using measures of visual fixation and visual scanning to study how infants with autism interact with the social world. Through a prospective study of the infant siblings of older children with autism, this project will measure the developmental course of altered social engagement in infants subsequently diagnosed with an autism spectrum disorder. The three goals of this project quantitative diagnostic markers, predictors of outcome, and endophenotypes capable of parsing the heterogeneity of the broader autism spectrum are also key objectives of the NIH Interagency Autism Committee. Like the Committee's action items, this project emphasizes developmental markers and screening in infants, as well as neurodevelopmental processes, and is, therefore, highly relevant to public health.